Synthesis of Enantioenriched 1,2‐cis Disubstituted Cycloalkanes by Convergent NiH Catalysis

Abstract

Enantioenriched multi‐substituted cycloalkanes constitute an essential class of compounds in pharmaceuticals, natural products and agrochemicals. Here we report an NiH‐catalyzed asymmetric migratory hydroalkylation process for the efficient and selective construction of such compounds. Through a dynamic kinetic asymmetric transformation (DYKAT), easily accessible racemic and isomeric mixtures of cycloalkenes could be directly utilized as starting materials, convergently producing thermo‐dynamically disfavored chiral 1,2‐cis disubstituted cycloalkanes bearing vicinal stereocenters with high levels of regio‐, diastereo‐ and enantioselectivity. In addition, prochiral cyclic alkenes can be also employed, and deliver chiral 1,2‐cis disubstituted cycloalkanes through desymmetrization process.

Nickel-Catalyzed Migratory Cross-Coupling Reactions: New Opportunities for Selective C–H Functionalization

“…Recently, through a dynamic kinetic asymmetric transformation (DYKAT), we were able to achieve a NiH-catalyzed asymmetric migratory hydroalkylation of easily accessible racemic and isomeric mixtures of cycloalkenes (Figure ). This DYKAT protocol provides a convenient approach toward the synthesis of a variety of enantioenriched but thermodynamically disfavored 1,2- cis -disubstituted cycloalkanes ( 39a – 39g ). The interaction between a pre-existing substituent (e.g., ester) in an olefinic substrate and a chiral catalyst plays an important role in the regio- and stereocontrol.…”

NiH-catalyzed C–N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons

“…The rise of NiH catalysis has notably shied the landscape of this eld. [48][49][50][51][52][53][54][55][56][57][58][59] While nickel has historically been valued as a competitive alternative to precious metals like palladium and platinum due to its catalytic properties, recent applications have elevated its signicance beyond being merely costeffective. The comparative analysis of CuH and NiH in hydroamination and hydroamidation reactions reveals their unique chemical properties and reactivities.…”

Nickel‐Catalyzed Regio‐ and Enantioselective Migratory Hydrocyanation of Internal Alkenes: Expanding the Scope to α,ω‐Diaryl Internal Alkenes

“…However, the selective functionalization of remote C(sp 3 )−H bonds in a regio‐ and enantioselective fashion still remains a long‐standing synthetic challenge [1b] . Owing to the difficulty of simultaneous control of both regio‐ and stereoselectivity, only a few examples have been reported wherein stereocenters featuring Bpin, [2] aryl, [3] alkyl, [4] acyl [5] substituents were smoothly constructed with high regioselectivity with the assistance of directing groups (DGs=aryl, ether, boron, etc.) near the C=C bonds of internal alkenes (Scheme 1a).…”